Cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), are molecules produced by a variety of cells, such as monocytes and macrophages, which have been identified as mediators of inflammatory processes. Interleukin-1 is a cytokine with a wide range of biological and physiological effects, including fever, prostaglandin synthesis (in e.g., fibroblasts, muscle and endothelial cells), T-lymphocyte activation, and interleukin 2 production.
cDNAs coding for two distinct forms of IL-1 have been isolated and expressed; these cDNAs represent two different gene products, termed IL-1β (Auron et al. (1984) Proc. Natl. Acad. Sci. USA 81:7909) and IL-1α (Lomedico et al. (1984) Nature 312:458). IL-1β is the predominant form produced by human monocytes both at the mRNA and protein level. The two forms of human IL-1 share only 26% amino acid homology. Despite their distinct polypeptide sequences, the two forms of IL-1 have structural similarities (Auron et al. (1985) J. Mol. Cell Immunol. 2:169), in that the amino acid homology is confined to discrete regions of the IL-1 molecule.
The two forms of IL-1 possess similar biological properties, including induction of fever, slow wave sleep, and neutrophilia, T- and B-lymphocyte activation, fibroblast proliferation, cytotoxicity for certain cells, induction of collagenases, synthesis of hepatic acute phase proteins, and increased production of colony stimulating factors and collagen. As such, both forms of IL-1 have been implicated in the pathophysiology of a variety of human diseases and disorders, including autoimmune and inflammatory diseases, e.g., multiple sclerosis (Brosnan et al. (1995). Neurology 45(6 suppl 6):
Antibodies capable of binding of IL-1α and IL-1β have been described in the art (see US Publication No. 20030040083 and PCT publication WO 07/063,308). However, there exists a need for improved therapeutics to IL-1α and IL-1β.